Structural highlights
Disease
COF2_HUMAN Typical nemaline myopathy. The disease is caused by variants affecting the gene represented in this entry.
Function
COF2_HUMAN Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. Its F-actin depolymerization activity is regulated by association with CSPR3 (PubMed:19752190). It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere (By similarity).[UniProtKB:P45591][1]
Publication Abstract from PubMed
Actin polymerization dynamics regulated by actin-binding proteins are essential for various cellular functions. The cofilin family of proteins are potent regulators of actin severing and filament disassembly. The structural basis for cofilin-isoform-specific severing activity is poorly understood as their high-resolution structures in complex with filamentous actin (F-actin) are lacking. Here, we present the atomic-resolution structure of the muscle-tissue-specific isoform, cofilin-2 (CFL2), assembled on ADP-F-actin, determined by magic-angle-spinning (MAS) NMR spectroscopy and data-guided molecular dynamics (MD) simulations. We observe an isoform-specific conformation for CFL2. This conformation is the result of a unique network of hydrogen bonding interactions within the alpha2 helix containing the non-conserved residue, Q26. Our results indicate F-site interactions that are specific between CFL2 and ADP-F-actin, revealing mechanistic insights into isoform-dependent F-actin disassembly.
Magic angle spinning NMR structure of human cofilin-2 assembled on actin filaments reveals isoform-specific conformation and binding mode.,Kraus J, Russell RW, Kudryashova E, Xu C, Katyal N, Perilla JR, Kudryashov DS, Polenova T Nat Commun. 2022 Apr 19;13(1):2114. doi: 10.1038/s41467-022-29595-9. PMID:35440100[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Papalouka V, Arvanitis DA, Vafiadaki E, Mavroidis M, Papadodima SA, Spiliopoulou CA, Kremastinos DT, Kranias EG, Sanoudou D. Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle. Mol Cell Biol. 2009 Nov;29(22):6046-58. doi: 10.1128/MCB.00654-09. Epub 2009 Sep , 14. PMID:19752190 doi:http://dx.doi.org/10.1128/MCB.00654-09
- ↑ Kraus J, Russell RW, Kudryashova E, Xu C, Katyal N, Perilla JR, Kudryashov DS, Polenova T. Magic angle spinning NMR structure of human cofilin-2 assembled on actin filaments reveals isoform-specific conformation and binding mode. Nat Commun. 2022 Apr 19;13(1):2114. doi: 10.1038/s41467-022-29595-9. PMID:35440100 doi:http://dx.doi.org/10.1038/s41467-022-29595-9
